Latin American Scientific Production on COVID-19 Vaccines

Background Currently, there is a worldwide health crisis due to the COVID-19 pandemic; consequently, it is necessary to find effective vaccines in order to immunize the population and prevent the transmission of the disease. Likewise, it is important to know vaccine progress and efficacy research, mainly in Latin American countries where no studies have been conducted yet to know the scientific production on COVID-19. Methods A retrospective and descriptive study was carried out and COVID-19 vaccine publications in Scopus-indexed journals were considered as a unit of analysis for the period between 2020 and June 2021, with authors affiliated to Latin American institutions. Results We found 141 published Scopus-indexed COVID-19 vaccine articles with authors affiliated to Latin American institutions. Brazil has the highest scientific production with 33.33%, followed by Mexico, Colombia, Argentina and Chile. Regarding productivity by institution, 137 international institutions have participated in the Latin American COVID-19 vaccine production. The journals with the highest number of published articles are Vaccines and Vaccine. Both journals are located in Q1 of the SJR. The most frequently used descriptor was coronavirus disease 2019. Conclusion The Latin American scientific production on COVID-19 vaccines included 141 published Scopus-indexed articles. Likewise, Brazil is the Latin American country with the highest scientific production.


INTRODUCTION
The world continues experiencing an unprecedented crisis due to the rapid spread of the new coronavirus . More than a year has passed since the beginning of the health emergency and there is no doubt about the revolution that has taken place in the field of research to find a cure, thus, rapid progress has been made in understanding the biology of SARS-CoV-2 and producing safe and effective vaccines (1). Currently, there are alternatives licensed and recommended by the World Health Organization (2).
In this case, an effective vaccine is crucial to prevent morbidity and mortality due to . Therefore, the objective in vaccine development is to evidence their efficacy to protect the world's population (3). In this regard, it was known that as of February 2021 there were 44 candidate vaccines in clinical phase and 154 in preclinical pase (4). With respect to their characteristics, most of them target the peak protein (S) of the virus (5), which is found on the surface of the SARS-CoV-2 envelope, allowing it to bind to a cellular receptor (angiotensinconverting enzyme 2) and penetrate host cells. In this regard, studies have shown that activating neutralizing antibodies against the S protein would provide protection against infection. Therefore, the peak protein represents the target of most of the vaccines developed in 2020.
Different technologies are currently being applied in vaccines, also known as platforms. These fall into two categories: whole virus-based and viral protein-based (6). Now, a remarkable issue is the speed with which they were developed, and this is due to different reasons such as the fact that the causative agent was quickly characterized and found to be relatively stable and that the immunity to the coronavirus family was already known, thus, previous research made possible the use of innovative vaccination platforms, and finally, due to the unprecedented scientific and financial deployment that made it possible for clinical trials to be conducted in record time (7). In that sense, platform, adjuvants, form of administration, age and pre-existing crossreactive immunity essentially determine safety, however, due to emergence of resistant variants it is possible that vaccines may need updating.
At this point, it is estimated that the world may return to a pre-pandemic state if a fairly equitable vaccination process is achieved among all countries (8), so it is important to recognize that the strongest predictor of COVID-19 vaccination intentions is to trust in the safety of the vaccines (9), even despite the existence of manageable systemic and local side effects (10). However, there is a large part of the population that does not want to be vaccinated, thus, researchers like Troiano and Nardi (9) studied the most frequent reasons for refusing vaccination, the most noteworthy being concerns about safety, thinking that a hastily produced vaccine is too dangerous, considering that the vaccine is useless due to harmless nature of COVID-19, doubts about the efficacy of the vaccine, doubts about the origin of the vaccine, among others. These facts have motivated researchers to develop measurement instruments such as a scale to measure the perception of SARS-CoV-2 vaccine acceptance (11).
In relation to the above, research results show that Vietnam, India, China, Denmark, South Korea, Serbia, Croatia, France, Lebanon and Paraguay are countries with populations that show a higher proportion of vaccine acceptance (12). However, in many Latin American countries there is still an unfavorable attitude, partly due to the role played by the media (13), and mainly, irrational beliefs and fatalistic ideas resulting from culture and scarce scientific information on vaccine importance (14,15).
In view of these facts, it is extremely important to analyze the scientific production on vaccines. Although the literature contains research that evaluates the scientific activity on COVID-19 in databases such as Scopus (16) and Web of Science (17), there are only vaccine studies that describe the current vaccine platforms (18), the current status of COVID-19 vaccines and therapies (19), but there are no studies that guide researchers on what has already been produced and what is being researched in order to address knowledge gaps through future research. Therefore, the objective of this study is to analyze the Latin American scientific production on COVID-19 vaccines.

MATERIALS AND METHODS
Study design: Retrospective descriptive study. The documents that served as source for the analysis came from the Scopus databases, during the period January 2020 to June 2021. The search equation was used to extract documents: "Vaccine" and its relation with the terms: "2019-nCoV" OR "SARS-CoV-2" OR "2019 novel coronavirus" OR "Covid-19" OR "Coronavirus disease 2019" in the fields of title, abstract and keywords considering only those documents that were written by authors mentioning affiliations with Latin American institutions. The variables of author, institution, country and keywords were normalized, since production indicators were generated from them. Data collection: Through this search strategy, 156 documents were retrieved, which were subjected to a process of metadata normalization and elimination of documents that did not deal with the subject. The final sample for analysis was composed of 141 documents. Data analysis: With the extracted documents, a database was organized in Microsoft Excel that included the following data: name of the signing authors, title of the publication, type of publication, affiliation institutions of the signing authors, journal of publication and country of publication. Finally, with the support of the VOSviewer software, a network was created with the main thematic axes associated with the key words of the publications.

RESULTS
A total of 141 published Scopus-indexed articles with authors affiliated to Latin American institutions were found. Five types of publishable documents were included in the analysis. Original articles represent the largest number of documentary production (n=71; 50.35%), followed by review articles (n=41;29.08%), letters to the editor (n=12;8.51%), editorial (n=12;8.51%) and finally Notes (n=5;3.55%). Vaccine publications during the last year increased by 26.24%.
Brazil is the Latin American country with the highest scientific production on vaccines, representing 33.33% of the Latin American production, followed by Mexico, Colombia, Argentina and Chile, countries with 10 or more publications during the period under evaluation. There are 05 Latin American countries (Dominican Republic, Puerto Rico, Costa Rica, Bolivia and Jamaica) with at least 01 publication (Table 1).   Table 3 lists the most productive journals, among which Vaccines and Vaccine stand out (more than 7 papers published). Both journals are located in Q1 of the SJR. Scientific production is concentrated in European and North American journals, and 90% of such journals are located in Q1. This demonstrates not only high visibility of the contributions but also their possible quality.  The ten most cited COVID-19 vaccine articles are presented. Eighty percent of them were published in 2020 and only two of the total number have been cited more than 100 times (Table 5).   . However, it is also important to know related research from other parts. Latin America is one of the regions most affected by COVID-19 in terms of cases and deaths, in addition to seriously affecting individuals' mental health (20). In this context, the objective of this research was to analyze the Latin American scientific production on COVID-19 vaccines.
Our results confirm that Latin America produced a total of 141 COVID-19 vaccine articles. This result compared with the world production of COVID-19 vaccine articles, which is 2,625 articles, where only Brazil appears in 15th place, far from the production of other countries such as China, the USA, the United Kingdom and Italy (17). The results are similar to those found in a study on the scientific production of mental health in the time of Covid-19, where the Latin American scientific production was 4.74% of the world production, which shows the scarce publication in Latin America (21).
Likewise, the bibliometric analysis carried out through this study has made it possible to characterize these researchers during the pandemic. Brazil has contributed the largest number of scientific publications on vaccines. This can be explained by the fact that Brazil hosts the largest number of top Latin American research centers and universities (22), and that Brazil is the country most affected by Covid-19(23) and despite the fact that its government has shown little importance in this area (24). Mexico occupies second place in the ranking. This can be explained by the fact that Mexico is the country with the second largest population (20) and also that together with Brazil they are leaders in scientific development and production at the Latin American level (25) and in Covid-19 production (26,27).
It is also important to highlight a significant number of authors who have taken advantage of the opportunity given by the pandemic and the importance of this to increase the number of studies published through letters to the editor, review articles and original articles (17).
With respect to the most cited journals in Scopus, Vaccines, Vaccine and Frontier In Immunology ranked 1 st , 2 nd and 3 rd , respectively. This could be due to the fact that they are journals of global scope, with a high impact factor, and with open calls for manuscripts on this topic. Additionally, as in the case of Vaccine, it is an important publication for Latin America (24). All these journals have a great scientific influence and although due to the speed of publications some retractions were found (26), they remain in the world top, which means a greater number of citations (27).
With an H-Index of 42, the most published author is Alfonso Rodriguez-Morales, Colombian, with 9 articles. He is among the authors who have also contributed the most number of COVID-19 studies (25). In terms of productivity by institutions, both USP (Brazil) and the Fundación Universitaria Autónoma de Las Américas (Colombia) lead in this category. It should be noted that the author Rodriguez-Morales belongs to the Colombian institution.
With 697 citations in Scopus, the published co-authored article with the highest impact was by Polack, Thomas, Kitchin et al. (28) that was published in The New England Journal of Medicine. This article aimed to report safety and efficacy findings from the phase 2/3 part of a global trial evaluating the safety, immunogenicity, and efficacy of the BNT162b2 mRNA COVID-19 vaccine for the prevention of COVID-19 disease in individuals aged 16 and older. The authors demonstrated that a two-dose regimen of BNT162b2 conferred 95% protection against COVID-19 in individuals aged 16 or older. In a bibliometric investigation of rabies vaccination over the past three decades, they concluded the importance of strengthening collaborative research between institutions and researchers in developing countries and developed countries (29).
Another key factor was the co-occurrence relationships between keyword pairs that were determined from the number of articles in the database. Cluster 01 (red) relates to research addressing the epidemic and factors conditioning immune response. Cluster 02 (green) analyzes the safety and efficacy of COVID-19 treatments. Cluster 03 (blue) highlights the COVID-19 vaccine characteristics to mitigate the epidemic. In a study conducted on Covid-19 vaccine research, the most used keywords were COVID and vaccine; also according to visualization mapping COVID-19 was the most co-occurring author keyword (30).
The findings of this research show that bibliometric studies characterize research conducted in Latin America. Through this design, the typology of publication, institutions, researchers, number of citations of scientific production are observed. In addition, the most analyzed groups with respect to the topic of COVID-19 vaccines are observed.
However, this bibliometric study has limitations. Only the Scopus database was used. Although it is a referential platform with broad coverage in science, we believe it is necessary to conduct similar research using other databases through additional studies. It is also important to note that the number of publications and citations (31) of co-authorship is increasing every day, so it is very difficult to keep a daily control, which we also consider to be a limitation. Therefore, the researchers determined a time frame for data collection and performing their research and discussion. It is possible that data may have been lost in the course of this process and that reality does not coincide with the data shown in this research.
Despite these limitations, we consider that this research contributes to the global thematic on the Covid-19 vaccine, finding articles published in different journals indexed in Scopus, which have links to institutions located in the top 10 of the Ibero-American ranking of Higher Education Institutions located in 17 Latin American countries.